Sensitive and multiplexed analysis of cancer biomarkers with QD barcodes

使用 QD 条形码对癌症生物标志物进行灵敏的多重分析

基本信息

批准号：
8197689
负责人：
Xiaohu Gao
金额：
$ 30.86万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-12-14 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8197689
关键词：
Achievement Adaptor Signaling Protein Affinity Animals Anus Area Award Binding Biological Biological Markers Biomedical Engineering Biosensor Caliber Cancer Detection Cells Chemicals Chemistry Clinical Code Collaborations Color Complex DNA DNA Microarray Chip DNA analysis Data Detection Development Diagnosis Diagnostic Disease Dyes ERBB2 gene Early Detection Research Network Engineering Environment Environmental Health Enzyme-Linked Immunosorbent Assay Epidermal Growth Factor Receptor Event Fluorescence Fostering Gene Expression Profiling Generations Genetic Genomics Goals Image Immobilization Individual Interdisciplinary Study Joints Label Laboratories Life Ligands Link Malignant Neoplasms Mass Spectrum Analysis Medical Methods Microfluidic Microchips Microspheres Modeling Molecular Molecular Analysis Molecular Profiling Mutation Nanosphere Nanostructures National Cancer Institute Nucleic Acids Oligonucleotides Optics Paper Pathology Patients Peptide antibodies Photobleaching Polymers Process Property Proteins Proteomics Publishing Quantum Dots RNA Reporter Research Research Design Research Methodology Research Personnel Resistance Sampling Science Screening for cancer Semiconductors Serum Signal Transduction Site Specificity Specimen Structure Surface System Techniques Technology Temperature Therapeutic Time Tissues Validation Yang absorption anticancer research base chemical bond college copolymer crosslink drug discovery experience flexibility graduate student improved innovation innovative technologies instrumentation light emission medical schools melting miniaturize molecular assembly/self assembly nano nanoparticle nanoscale nanotoxicology new technology novel novel strategies optical imaging prognostic protein profiling research study seal self assembly single molecule therapeutic target tumor

项目摘要

Cancer is recognized as a highly complex disease involving myriad molecular processes and arises as the result of gradual accumulation of multiple genetic and proteomic alterations, which also serve as cancer biomarkers. A major focus of current cancer research is how to correlate these underlying molecular events with cancer development and progression. Recent advances in cancer molecular analysis and bioanalytical sciences have led to the development of DNA chips, ELISA, miniaturized biosensors, microfluidic devices (e.g., bioMEMS or microelectromechanical systems, and mass spectrometry. These enabling technologies have substantially influenced the way that we detect and analyze cancer, such as gene expression profiling, drug discovery, and clinical diagnostics. However, none of these technical platforms are sufficiently flexible to allow detection of both genetic alterations and protein profiles with sensitivity down to single molecule level. As current research in genomics and proteomics produces more sequence data, there is a strong need for new technologies that can rapidly screen a large number of nucleic acids and proteins. In this context, the primary goal of this proposal is to develop a versatile and sensitive technology that can quickly analyze cancer molecular profiles (such as DNAs, RNAs and proteins) in a highly multiplexed manner for accurate diagnostics, prognostics and effective therapeutics. The innovation and basic rationale of this technology lies in the novel optical properties of semiconductor quantum dots or QDs (e.g., tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple colors) and our ability to make optical barcodes using these nanoparticles. Different from single QD based imaging, we propose to prepare QD encoded optical barcodes of both micrometer sizes and nanometer sizes. The micro-barcodes will be used to tag biomolecular probes, whereas the nanospheres will be used as reporters to enhance the current detection sensitivity by 2-3 orders of magnitude. We will also explore new surface encapsulation and pore sealing approaches to stabilize the optical barcodes, and chemical conjugation approaches to optimize biomolecular probe immobilization. We will further carry out experiments to detect mutations on both DNA and RNA level as well as the profiles of protein cancer biomarkers, which can be isolated from serum or homogenized cell and tissue specimens.

癌症被认为是一种高度复杂的疾病，涉及无数的分子过程，并随着多种遗传和蛋白质组改变逐渐积累的结果，这些改变也可作为癌症生物标志物。当前癌症研究的一个主要焦点是如何关联这些潜在的分子事件随着癌症的发展和进展。癌症分子分析和生物分析的最新进展科学促进了 DNA 芯片、ELISA、微型生物传感器、微流体装置的发展（例如，生物MEMS或微机电系统以及质谱法。这些使能技术极大地影响了我们检测和分析癌症的方式，例如基因表达谱，药物发现和临床诊断。然而，这些技术平台都不够灵活允许检测遗传改变和蛋白质谱，灵敏度低至单分子等级。随着当前基因组学和蛋白质组学研究产生更多的序列数据，强烈需要寻找能够快速筛选大量核酸和蛋白质的新技术。在这种背景下，该提案的主要目标是开发一种多功能且敏感的技术，可以在高度多重分析中快速分析癌症分子谱（例如 DNA、RNA 和蛋白质）准确诊断、预测和有效治疗的方式。创新点及基本原理这项技术的关键在于半导体量子点或 QD 的新颖光学特性（例如，可调谐光发射、提高信号亮度、抗光漂白和同时激发多种颜色）以及我们使用这些纳米粒子制作光学条形码的能力。与单身不同基于 QD 的成像，我们建议制备微米尺寸和纳米尺寸。微型条形码将用于标记生物分子探针，而纳米球将用于标记生物分子探针。用作报告基因可使当前检测灵敏度提高2-3个数量级。我们也会探索新的表面封装和孔隙密封方法来稳定光学条形码，以及优化生物分子探针固定的化学缀合方法。我们将进一步开展检测 DNA 和 RNA 水平突变以及蛋白质癌症概况的实验生物标志物，可以从血清或均质细胞和组织样本中分离出来。

项目成果

期刊论文数量（25）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Designing multifunctional quantum dots for bioimaging, detection, and drug delivery.

设计用于生物成像、检测和药物输送的多功能量子点。

DOI：
10.1039/b915139g
发表时间：
2010-11
期刊：
Chemical Society reviews
影响因子：
46.2
作者：
Zrazhevskiy P;Sena M;Gao X
通讯作者：
Gao X

Trapping and dynamic manipulation of polystyrene beads mimicking circulating tumor cells using targeted magnetic/photoacoustic contrast agents.

使用靶向磁/光声造影剂模拟循环肿瘤细胞的聚苯乙烯珠的捕获和动态操作。

DOI：
发表时间：
2012-10
期刊：
影响因子：
3.5
作者：
Wei, Chen;Xia, Jinjun;Pelivanov, Ivan;Hu, Xiaoge;Gao, Xiaohu;O'Donnell, Matthew
通讯作者：
O'Donnell, Matthew

Real-time integrated photoacoustic and ultrasound (PAUS) imaging system to guide interventional procedures: ex vivo study.

用于指导介入手术的实时集成光声和超声（PAUS）成像系统：离体研究。

DOI：
发表时间：
2015-02
期刊：
影响因子：
0
作者：
Wei, Chen;Nguyen, Thu;Xia, Jinjun;Arnal, Bastien;Wong, Emily Y;Pelivanov, Ivan M;O'Donnell, Matthew
通讯作者：
O'Donnell, Matthew

Eliminating Size-Associated Diffusion Constraints for Rapid On-Surface Bioassays with Nanoparticle Probes.

使用纳米颗粒探针消除快速表面生物测定中与尺寸相关的扩散限制。